Hypoxia inducible transcription in antitumor strategies

求职者：我的职业目标是成为一名独立的内科医生兼科学家，主要专注于以下研究 了解肿瘤发生的机制基础及其在临床中的应用 这些知识对发展合理的癌症治疗方法具有重要意义。这个 希望这样的研究不仅能增进人们的理解， 儿童恶性肿瘤的治疗，在那里我已经完成了我的 临床团契，但在肿瘤学上也是有用的。对于 在不久的将来，霍华德·特明奖将极大地帮助我过渡到 作为一名分子癌症科学家完全独立，通过为 在大卫博士的指导下，未来1-2年继续研究 利文斯顿。在这一点上，我计划过渡到完全 独立的立场。 环境：达纳-法伯癌症研究所和哈佛医学院 为完成以下任务提供良好的协作环境 本提案中概述的研究和培训目标，在 有指导和无指导阶段的赠款。有现成的访问国家的途径- DFCI和HMS的最先进的设备、设施和核心服务。 利文斯顿博士被广泛认为是一位优秀的科学导师，他的 实验室提供完全支持和激励的智力和 科学环境。 研究：该方案的具体目标是：1.确定机制 通过破坏低氧诱导的转录导致抗肿瘤 效果。2.寻找专门干扰缺氧的小分子-- 有反应的转录。3.尝试创建基于机制的成像 低氧反应抑制剂在动物体内作用的研究方法 肿瘤。

DESCRIPTION (provided by applicant): Candidate: My career goal is to become an independent physician-scientist with a primary focus on research aimed at understanding the mechanistic bases for tumorigenesis and the application of such knowledge to the development of rational therapeutics for cancer. The hope would be that such research would not only advance the understanding and treatment of pediatric malignancies, where I have already completed my clinical fellowship, but also be of utility in oncology in general. For the immediate future, the Howard Temin Award would greatly assist my transition to full independence as a molecular cancer scientist by providing support for the next 1-2 years of continued research under the mentorship of Dr. David Livingston. At that point, I would plan to undertake a transition to a fully independent position. Environment: The Dana-Farber Cancer Institute and Harvard Medical School provide excellent collaborative environments for the completion of the research and training goals outlined in this proposal, both during the mentored and unmentored phases of the grant. There is ready access to state- of-the-art equipment, facilities, and core services both at the DFCI and HMS. Dr. Livingston is widely regarded as an excellent scientific mentor, and his laboratory provides a wholly supportive and stimulating intellectual and scientific environment. Research: The specific aims of this proposal are: 1. Determine the mechanism whereby disruption of hypoxia-inducible transcription leads to an anti-tumor effect. 2. Search for small molecules that specifically perturb hypoxia- responsive transcription. 3. Attempt to create a mechanism-based imaging method for studying the effect of hypoxia-response inhibitors in animal tumors.